Ethanol-induced alterations in neurotrophin expression in developing cerebellum: Relationship to periods of temporal susceptibility
Ethanol-induced alterations in neurotrophin expression in developing cerebellum: Relationship to periods of temporal susceptibility
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DOI：
10.1097/00000374-199910000-00011
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发表时间：
1999-10-01
影响因子：
3.2
通讯作者：
Paiva, M
中科院分区：
文献类型：
--
作者：
Heaton, MB;Mitchell, JJ;Paiva, M
背景：发育中的小脑已被证明受到乙醇暴露的深刻影响，并表现出一种暂时的脆弱性模式。小脑浦肯野细胞在出生后第4天或第5天对乙醇特别敏感（P4-5），而在出生后稍晚的时期，这一群体对类似的乙醇损伤的敏感性要低得多（P7-9）。该研究的目的是确定神经营养因子的差异改变是否与这种差异易感性有关。方法：将新生大鼠雾化吸入乙醇，采用酶联免疫吸附法测定其小脑神经生长因子、脑源性神经营养因子。以及神经营养素-3蛋白含量。这些分析是在小脑乙醇敏感性最大的时期（出生后4-5天[P4-5]）、敏感性低得多的时期（P7-8）和整个“大脑生长突增”期间（P4-10）暴露于乙醇后进行的。结果：这些测定结果显示，暴露于P4-5后，乙醇诱导的小脑神经生长因子显著减少，而暴露于P7-8或P4-10后，乙醇诱导的小脑神经生长因子减少不明显。脑源性神经营养因子和神经营养因子-3均未见明显变化。结论：这些结果表明，神经生长因子的改变，先前已被证明支持小脑浦肯野细胞和颗粒细胞，可能是促进这些神经元群体早期乙醇易感性的机制。
Background: The developing cerebellum has been shown to be profoundly affected by exposure to ethanol and to exhibit a temporal pattern of vulnerability. Cerebellar Purkinje cells are particularly susceptible to ethanol on postnatal day 4 or day 5 (P4-5), whereas this population is much less vulnerable to similar ethanol insult slightly later in the postnatal period (P7-9). The purpose of the study was to determine whether differential alterations in neurotrophic factors might be associated with this differential susceptibility.Methods: Neonatal rats were exposed to ethanol via vapor inhalation, and enzyme-linked immunoabsorbent assays were subsequently conducted to assess cerebellar nerve growth factor, brain-derived neurotrophic factor. and neurotrophin-3 protein content. These analyses were made after ethanol exposure during the period of maximal cerebellar ethanol sensitivity (postnatal days 4-5 [P4-5]), during a period of much lower sensitivity (P7-8), and during the entire "brain growth spurt" (P4-10).Results: These determinations revealed a significant ethanol-induced decrease in cerebellar nerve growth factor after exposure on P4-5 but not after exposure on P7-8 or P4-10. No significant changes in brain-derived neurotrophic factor or neurotrophin-3 were found with any of the exposure paradigms.Conclusions: These results suggest that alterations in nerve growth factor, which has previously been shown to support cerebellar Purkinje and granule cells, may be a mechanism contributing to the early ethanol susceptibility within these neuronal populations.